tbuckley/cabot-search huggingface dataset:
A novel through-the-scope helix tack-and-suture device for mucosal defect closure following colorectal endoscopic submucosal dissection: a multicenter study
Authors: Jad Farha, Hemchand Ramberan, Hiroyuki Aihara, Linda Y. Zhang, Amit Mehta, Camille Hage, Alexander Schlachterman, Anand Kumar, Brianna Shinn, Andrew Canakis, Raymond E. Kim, Lionel S. DʼSouza, Jonathan M. Buscaglia, Andrew C. Storm, Jason Samarasena, Kenneth Chang, Shai Friedland, Peter V. Draganov, Bashar J. Qumseya, Salmaan Jawaid, Mohamed O. Othman, Muhammad K. Hasan, Dennis Yang, Mouen A. Khashab, Saowanee Ngamruengphong
Journal: Endoscopy (2022)

Background Complete closure of large mucosal defects following colorectal endoscopic submucosal dissection (ESD) with through-the-scope (TTS) clips is oftentimes not possible. We aimed to report our early experience of using a novel TTS suturing system for the closure of large mucosal defects after colorectal ESD. Methods We performed a retrospective multicenter cohort study of consecutive patients who underwent attempted prophylactic defect closure using the TTS suturing system after colorectal ESD. The primary outcome was technical success in achieving complete defect closure, defined as a &lt; 5 mm residual mucosal defect in the closure line using TTS suturing, with or without adjuvant TTS clips. Results 82 patients with a median defect size of 30 (interquartile range 25–40) mm were included. Technical success was achieved in 92.7 % (n = 76): TTS suturing only in 44 patients (53.7 %) and a combination of TTS suturing to approximate the widest segment followed by complete closure with TTS clips in 32 (39.0 %). Incomplete/partial closure, failure of appropriate TTS suture deployment, and the need for over-the-scope salvage closure methods were observed in 7.3 % (n = 6). One intraprocedural bleed, one delayed bleed, and three intraprocedural perforations were observed. There were no adverse events related to placement of the TTS suture. Conclusion The TTS suture system is an effective and safe tool for the closure of large mucosal defects after colorectal ESD and is an alternative when complete closure with TTS clips alone is not possible.
A <i>RUNX1</i>-FPDMM rhesus macaque model reproduces the human phenotype and predicts challenges to curative gene therapies
Authors: Byung-Chul Lee, Yifan Zhou, Erica Bresciani, Neval Ozkaya, Alina Dulau-Florea, Blake Carrington, Tae-Hoon Shin, Valentina Baena, Zulfeqhar A. Syed, So Gun Hong, Tao Zhen, Katherine R. Calvo, Paul Liu, Cynthia E. Dunbar
Journal: Blood (2022)
Glycemic Index Versus Wheat Fiber on Arterial Wall Damage in Diabetes: A Randomized Controlled Trial
Authors: David J.A. Jenkins, Laura Chiavaroli, Arash Mirrahimi, Sandra Mitchell, Dorothea Faulkner, Sandhya Sahye-Pudaruth, Melanie Paquette, Judy Coveney, Omodele Olowoyeye, Darshna Patel, Sathish Chandra Pichika, Balachandran Bashyam, Tishan Maraj, Chantal Gillett, Russell J. de Souza, Livia S.A. Augustin, Sonia Blanco Mejia, Stephanie K. Nishi, Lawrence A. Leiter, Robert G. Josse, Gail E. McKeown-Eyssen, Alan R. Berger, Philip W. Connelly, Korbua Srichaikul, Cyril W.C. Kendall, John L. Sievenpiper, Alan R. Moody
Journal: Diabetes Care (2022)

High cereal fiber and low-glycemic index (GI) diets are associated with reduced cardiovascular disease (CVD) risk in cohort studies. Clinical trial evidence on event incidence is lacking. Therefore, to make trial outcomes more directly relevant to CVD, we compared the effect on carotid plaque development in diabetes of a low-GI diet versus a whole-grain wheat-fiber diet.
A Therapeutically Targetable NOTCH1–SIRT1–KAT7 Axis in T-cell Leukemia
Authors: Olga Lancho, Amartya Singh, Victoria da Silva-Diz, Maya Aleksandrova, Jesminara Khatun, Luca Tottone, Patricia Renck Nunes, Shirley Luo, Caifeng Zhao, Haiyan Zheng, Eric Chiles, Zhenyu Zuo, Pedro P. Rocha, Xiaoyang Su, Hossein Khiabanian, Daniel Herranz
Journal: Blood Cancer Discovery (2022)

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is a NOTCH1-driven disease in need of novel therapies. Here, we identify a NOTCH1–SIRT1–KAT7 link as a therapeutic vulnerability in T-ALL, in which the histone deacetylase SIRT1 is overexpressed downstream of a NOTCH1-bound enhancer. SIRT1 loss impaired leukemia generation, whereas SIRT1 overexpression accelerated leukemia and conferred resistance to NOTCH1 inhibition in a deacetylase-dependent manner. Moreover, pharmacologic or genetic inhibition of SIRT1 resulted in significant antileukemic effects. Global acetyl proteomics upon SIRT1 loss uncovered hyperacetylation of KAT7 and BRD1, subunits of a histone acetyltransferase complex targeting H4K12. Metabolic and gene-expression profiling revealed metabolic changes together with a transcriptional signature resembling KAT7 deletion. Consistently, SIRT1 loss resulted in reduced H4K12ac, and overexpression of a nonacetylatable KAT7-mutant partly rescued SIRT1 loss-induced proliferation defects. Overall, our results uncover therapeutic targets in T-ALL and reveal a circular feedback mechanism balancing deacetylase/acetyltransferase activation with potentially broad relevance in cancer. Significance: We identify a T-ALL axis whereby NOTCH1 activates SIRT1 through an enhancer region, and SIRT1 deacetylates and activates KAT7. Targeting SIRT1 shows antileukemic effects, partly mediated by KAT7 inactivation. Our results reveal T-ALL therapeutic targets and uncover a rheostat mechanism between deacetylase/acetyltransferase activities with potentially broader cancer relevance. This article is highlighted in the In This Issue feature, p. 1
FOXA2 drives lineage plasticity and KIT pathway activation in neuroendocrine prostate cancer
Authors: Ming Han, Fei Li, Yehan Zhang, Pengfei Dai, Juan He, Yunguang Li, Yiqin Zhu, Junke Zheng, Hai Huang, Fan Bai, Dong Gao
Journal: Cancer Cell (2022)

Prostate cancer adeno-to-neuroendocrine lineage transition has emerged as a mechanism of targeted therapeutic resistance. Identifying the direct molecular drivers and developing pharmacological strategies using clinical-grade inhibitors to overcome lineage transition-induced therapeutic resistance are imperative. Here, using single-cell multiomics analyses, we investigate the dynamics of cellular heterogeneity, transcriptome regulation, and microenvironmental factors in 107,201 cells from genetically engineered mouse prostate cancer samples with complete time series of tumor evolution seen in patients. We identify that FOXA2 orchestrates prostate cancer adeno-to-neuroendocrine lineage transition and that Foxa2 expression is significantly induced by androgen deprivation. Moreover, Foxa2 knockdown induces the reversal of adeno-to-neuroendocrine transition. The KIT pathway is directly regulated by FOXA2 and specifically activated in neuroendocrine prostate cancer (NEPC). Pharmacologic inhibition of KIT pathway significantly suppresses mouse and human NEPC tumor growth. These findings reveal that FOXA2 drives adeno-to-neuroendocrine lineage plasticity in prostate cancer and provides a potential pharmacological strategy for castration-resistant NEPC.
circCAPRIN1 interacts with STAT2 to promote tumor progression and lipid synthesis via upregulating ACC1 expression in colorectal cancer
Authors: Yufei Yang, Dakui Luo, Yang Shao, Zezhi Shan, Qi Liu, Junyong Weng, Weijing He, Ruoxin Zhang, Qingguo Li, Ziliang Wang, Xinxiang Li
Journal: Cancer Communications (2022)

Abstract Background Circular RNAs (circRNAs) generated by back‐splicing of precursor mRNAs (pre‐mRNAs) are often aberrantly expressed in cancer cells. Accumulating evidence has revealed that circRNAs play a critical role in the progression of several cancers, including colorectal cancer (CRC). However, the current understandings of the emerging functions of circRNAs in CRC lipid metabolism and the underlying molecular mechanisms are still limited. Here, we aimed to explore the role of circCAPRIN1 in regulating CRC lipid metabolism and tumorigenesis. Methods circRNA microarray was performed with three pairs of tumor and non‐tumor tissues from CRC patients. The expression of circRNAs were determined by quantitative PCR (qPCR) and in situ hybridization (ISH). The endogenous levels of circRNAs in CRC cells were manipulated by transfection with lentiviruses overexpressing or silencing circRNAs. The regulatory roles of circRNAs in the occurrence of CRC were investigated both in vitro and in vivo using gene expression array, RNA pull‐down/mass spectrometry, RNA immunoprecipitation assay, luciferase reporter assay, chromatin immunoprecipitation analysis, and fluorescence in situ hybridization (FISH). Results Among circRNAs, circCAPRIN1 was most significantly upregulated in CRC tissue specimens. circCAPRIN1 expression was positively correlated with the clinical stage and unfavorable prognosis of CRC patients. Downregulation of circCAPRIN1 suppressed proliferation, migration, and epithelial‐mesenchymal transition of CRC cells, while circCAPRIN1 overexpression had opposite effects. RNA sequencing and gene ontology analysis indicated that circCAPRIN1 upregulated the expressions of genes involved in CRC lipid metabolism. Moreover, circCAPRIN1 promoted lipid synthesis by enhancing Acetyl‐CoA carboxylase 1 (ACC1) expression. Further mechanistic assays demonstrated that circCAPRIN1 directly bound signal transducer and activator of transcription 2 (STAT2) to activate ACC1 transcription, thus regulating lipid metabolism and facilitating CRC tumorigenesis. Conclusions These findings revealed the oncogenic role and mechanism of circCAPRIN1 in CRC. circCAPRIN1 interacted with STAT2 to promote CRC tumor progression and lipid synthesis by enhancing the expression of ACC1. circCAPRIN1 may be considered as a novel potential diagnostic and therapeutic target for CRC patients.
POMDP-Based Real-Time Path Planning for Manipulation of Multiple Microparticles via Optoelectronic Tweezers
Authors: Jiaxin Liu, Huaping Wang, Menghua Liu, Ran Zhao, Yanfeng Zhao, Tao Sun, Qing Shi
Journal: Cyborg and Bionic Systems (2022)

With high throughput and high flexibility, optoelectronic tweezers (OETs) hold huge potential for massively parallel micromanipulation. However, the trajectory of the virtual electrode has been planned in advance in most synchronous manipulations for multiple targets based on an optically induced dielectrophoresis (ODEP) mechanism, which is insufficient to ensure the stability and efficiency in an environment with potential collision risk. In this paper, a synchronously discretized manipulation method based on a centralized and decoupled path planner is proposed for transporting microparticles of different types with an OET platform. An approach based on the Kuhn-Munkres algorithm is utilized to achieve the goal assignment between target microparticles and goal positions. With the assistance of a visual feedback module, a path planning approach based on the POMDP algorithm dynamically determines the motion strategies of the particle movement to avoid potential collisions. The geometrical parameters of the virtual electrodes are optimized for different types of particles with the goal of maximum transport speed. The experiments of micropatterning with different morphologies and transporting multiple microparticles (e.g., polystyrene microspheres and 3T3 cells) to goal positions are performed. These results demonstrate that the proposed manipulation method based on optoelectronic tweezers is effective for multicell transport and promises to be used in biomedical manipulation tasks with high flexibility and efficiency.
Respiratory system mechanics, gas exchange, and outcomes in mechanically ventilated patients with COVID-19-related acute respiratory distress syndrome: a systematic review and meta-analysis
Authors: Mallikarjuna Ponnapa Reddy, Ashwin Subramaniam, Clara Chua, Ryan Ruiyang Ling, Christopher Anstey, Kollengode Ramanathan, Arthur S Slutsky, Kiran Shekar
Journal: The Lancet Respiratory Medicine (2022)
Fee for home delivery and monitoring of antiretroviral therapy for HIV infection compared with standard clinic-based services in South Africa: a randomised controlled trial
Authors: Ruanne V Barnabas, Adam A Szpiro, Xolani Ntinga, Melissa Latigo Mugambi, Heidi van Rooyen, Andrew Bruce, Philip Joseph, Thulani Ngubane, Meighan L Krows, Torin T Schaafsma, Theodore Zhao, Frank Tanser, Jared M Baeten, Connie Celum, Alastair van Heerden, Siyabonga Nkala
Journal: The Lancet HIV (2022)
Incidence and management of inflammatory arthritis in England before and during the COVID-19 pandemic: a population-level cohort study using OpenSAFELY
Authors: Mark D Russell, James B Galloway, Colm D Andrews, Brian MacKenna, Ben Goldacre, Amir Mehrkar, Helen J Curtis, Ben Butler-Cole, Thomas O'Dwyer, Sumera Qureshi, Joanna M Ledingham, Arti Mahto, Andrew I Rutherford, Maryam A Adas, Edward Alveyn, Sam Norton, Andrew P Cope, Katie Bechman
Journal: The Lancet Rheumatology (2022)
Effect of resistance to third-generation cephalosporins on morbidity and mortality from bloodstream infections in Blantyre, Malawi: a prospective cohort study
Authors: Rebecca Lester, Patrick Musicha, Kondwani Kawaza, Josephine Langton, James Mango, Helen Mangochi, Winnie Bakali, Oliver Pearse, Jane Mallewa, Brigitte Denis, Sithembile Bilima, Stephen B Gordon, David G Lalloo, Christopher P Jewell, Nicholas A Feasey
Journal: The Lancet Microbe (2022)
Incidence, Management, and Outcomes of Very Early Onset Inflammatory Bowel Diseases and Infantile-Onset Disease: An Epi-IIRN Study
Authors: Ohad Atia, Eric I. Benchimol, Natan Ledderman, Shira Greenfeld, Revital Kariv, Yiska Loewenberg Weisband, Eran Matz, Jacob Ollech, Iris Dotan, Amit Assa, Dror S. Shouval, Holm H. Uhlig, Aleixo M. Muise, Ola Olén, M. Ellen Kuenzig, Gilaad G. Kaplan, Dan Turner
Journal: Clinical Gastroenterology and Hepatology (2022)
Harnessing the synergy of perfusable muscle flap matrix and adipose-derived stem cells for prevascularization and macrophage polarization to reconstruct volumetric muscle loss
Authors: Qixu Zhang, Yulun Chiu, Youbai Chen, Yewen Wu, Lina W. Dunne, Rene D. Largo, Edward I. Chang, David M. Adelman, Mark V. Schaverien, Charles E. Butler
Journal: Bioactive Materials (2022)

Muscle flaps must have a strong vascular network to support a large tissue volume and ensure successful engraftment. We developed porcine stomach musculofascial flap matrix (PDSF) comprising extracellular matrix (ECM) and intact vasculature. PDSF had a dominant vascular pedicle, microcirculatory vessels, a nerve network, well-retained 3-dimensional (3D) nanofibrous ECM structures, and no allo- or xenoantigenicity. In-depth proteomic analysis demonstrated that PDSF was composed of core matrisome proteins (e.g., collagens, glycoproteins, proteoglycans, and ECM regulators) that, as shown by Gene Ontology term enrichment analysis, are functionally related to musculofascial biological processes. Moreover, PDSF−human adipose-derived stem cell (hASC) synergy not only induced monocytes towards IL-10−producing M2 macrophage polarization through the enhancement of hASCs' paracrine effect but also promoted the proliferation and interconnection of both human skeletal muscle myoblasts (HSMMs) and human umbilical vein endothelial cells (HUVECs) in static triculture conditions. Furthermore, PDSF was successfully prevascularized through a dynamic perfusion coculture of hASCs and HUVECs, which integrated with PDSF and induced the maturation of vascular networks in vitro. In a xenotransplantation model, PDSF demonstrated myoconductive and immunomodulatory properties associated with the predominance of M2 macrophages and regulatory T cells. In a volumetric muscle loss (VML) model, prevascularized PDSF augmented neovascularization and constructive remodeling, which was characterized by the predominant infiltration of M2 macrophages and significant musculofascial tissue formation. These results indicate that hASCs' integration with PDSF enhances the cells' dual function in immunomodulation and angiogenesis. Owing in part to this PDSF-hASC synergy, our platform shows promise for vascularized muscle flap engineering for VML reconstruction.
2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases
Authors: George E Fragoulis, Elena Nikiphorou, Mrinalini Dey, Sizheng Steven Zhao, Delphine Sophie Courvoisier, Laurent Arnaud, Fabiola Atzeni, Georg MN Behrens, Johannes WJ Bijlsma, Peter Böhm, Costas A Constantinou, Silvia Garcia-Diaz, Meliha Crnkic Kapetanovic, Kim Lauper, Mariana Luís, Jacques Morel, György Nagy, Eva Polverino, Jef van Rompay, Marco Sebastiani, Anja Strangfeld, Annette de Thurah, James Galloway, Kimme L Hyrich
Journal: Annals of the Rheumatic Diseases (2022)

Objectives To develop EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in patients with autoimmune inflammatory rheumatic diseases (AIIRD). Methods An international Task Force (TF) (22 members/15 countries) formulated recommendations, supported by systematic literature review findings. Level of evidence and grade of recommendation were assigned for each recommendation. Level of agreement was provided anonymously by each TF member. Results Four overarching principles (OAP) and eight recommendations were developed. The OAPs highlight the need for infections to be discussed with patients and with other medical specialties, in accordance with national regulations. In addition to biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for which screening for latent tuberculosis (TB) should be performed, screening could be considered also before conventional synthetic DMARDs, glucocorticoids and immunosuppressants. Interferon gamma release assay should be preferred over tuberculin skin test, where available. Hepatitis B (HBV) antiviral treatment should be guided by HBV status defined prior to starting antirheumatic drugs. All patients positive for hepatitis-C-RNA should be referred for antiviral treatment. Also, patients who are non-immune to varicella zoster virus should be informed about the availability of postexposure prophylaxis should they have contact with this pathogen. Prophylaxis against Pneumocystis jirovecii seems to be beneficial in patients treated with daily doses &gt;15–30 mg of prednisolone or equivalent for &gt;2–4 weeks. Conclusions These recommendations provide guidance on the screening and prevention of chronic and opportunistic infections. Their adoption in clinical practice is recommended to standardise and optimise care to reduce the burden of opportunistic infections in people living with AIIRD.
Adipose tissue macrophages exert systemic metabolic control by manipulating local iron concentrations
Authors: Nolwenn Joffin, Christy M. Gliniak, Jan-Bernd Funcke, Vivian A. Paschoal, Clair Crewe, Shiuhwei Chen, Ruth Gordillo, Christine M. Kusminski, Da Young Oh, Werner J. Geldenhuys, Philipp E. Scherer
Journal: Nature Metabolism (2022)
Metformin increases natural killer cell functions in head and neck squamous cell carcinoma through CXCL1 inhibition
Authors: McKenzie Crist, Benyamin Yaniv, Sarah Palackdharry, Maria A Lehn, Mario Medvedovic, Timothy Stone, Shuchi Gulati, Vidhya Karivedu, Michael Borchers, Bethany Fuhrman, Audrey Crago, Joseph Curry, Ubaldo Martinez-Outschoorn, Vinita Takiar, Trisha M Wise-Draper
Journal: Journal for ImmunoTherapy of Cancer (2022)

Metformin slows tumor growth and progression in vitro, and in combination with chemoradiotherapy, resulted in high overall survival in patients with head and neck cancer squamous cell carcinoma (HNSCC) in our phase 1 clinical trial (NCT02325401). Metformin is also postulated to activate an antitumor immune response. Here, we investigate immunologic effects of metformin on natural killer (NK) and natural killer T cells, including results from two phase I open-label studies in patients with HNSCC treated with metformin (NCT02325401, NCT02083692).Peripheral blood was collected before and after metformin treatment or from newly diagnosed patients with HNSCC. Peripheral immune cell phenotypes were evaluated using flow cytometry, cytokine expression by ELISA and/or IsoLight, and NK cell-mediated cytotoxicity was determined with a flow-based NK cell cytotoxicity assay (NKCA). Patient tumor immune infiltration before and after metformin treatment was analyzed with immunofluorescence. NK cells were treated with either vehicle or metformin and analyzed by RNA sequencing (RNA-seq). NK cells were then treated with inhibitors of significant pathways determined by RNA-seq and analyzed by NKCA, ELISA, and western blot analyses.Increased peripheral NK cell activated populations were observed in patients treated with metformin. NK cell tumor infiltration was enhanced in patients with HNSCC treated with metformin preoperatively. Metformin increased antitumorigenic cytokines ex vivo, including significant increases in perforin. Metformin increased HNSCC NK cell cytotoxicity and inhibited the CXCL1 pathway while stimulating the STAT1 pathway within HNSCC NK cells. Exogenous CXCL1 prevented metformin-enhanced NK cell-mediated cytotoxicity. Metformin-mediated NK cell cytotoxicity was found to be AMP-activated protein kinase independent, but dependent on both mechanistic target of rapamycin and pSTAT1.Our data identifies a new role for metformin-mediated immune antitumorigenic function through NK cell-mediated cytotoxicity and downregulation of CXCL1 in HNSCC. These findings will inform future immunomodulating therapies in HNSCC.
Cardiac implantable electronic device infections: impact of initiation of antimicrobial treatment before or after device removal on microbiological yield
Authors: Giacomo Ponta, Martina Ranzenigo, Alessandra Marzi, Chiara Oltolini, Chiara Tassan Din, Vincenzo Spagnuolo, Patrizio Mazzone, Silvia Carletti, Nicasio Mancini, Caterina Uberti-Foppa, Paolo Della Bella, Paolo Scarpellini, Antonella Castagna, Marco Ripa
Journal: Clinical Microbiology and Infection (2022)
Selective advantage of epigenetically disrupted cancer cells via phenotypic inertia
Authors: Ioannis Loukas, Fabrizio Simeoni, Marta Milan, Paolo Inglese, Harshil Patel, Robert Goldstone, Philip East, Stephanie Strohbuecker, Richard Mitter, Bhavik Talsania, Wenhao Tang, Colin D.H. Ratcliffe, Erik Sahai, Vahid Shahrezaei, Paola Scaffidi
Journal: Cancer Cell (2022)

The evolution of established cancers is driven by selection of cells with enhanced fitness. Subclonal mutations in numerous epigenetic regulator genes are common across cancer types, yet their functional impact has been unclear. Here, we show that disruption of the epigenetic regulatory network increases the tolerance of cancer cells to unfavorable environments experienced within growing tumors by promoting the emergence of stress-resistant subpopulations. Disruption of epigenetic control does not promote selection of genetically defined subclones or favor a phenotypic switch in response to environmental changes. Instead, it prevents cells from mounting an efficient stress response via modulation of global transcriptional activity. This "transcriptional numbness" lowers the probability of cell death at early stages, increasing the chance of long-term adaptation at the population level. Our findings provide a mechanistic explanation for the widespread selection of subclonal epigenetic-related mutations in cancer and uncover phenotypic inertia as a cellular trait that drives subclone expansion.
An emerging role of astrocytes in aging/neuroinflammation and gut-brain axis with consequences on sleep and sleep disorders
Authors: Sergey V. Gudkov, Dmitriy E. Burmistrov, Elena V. Kondakova, Ruslan M. Sarimov, Roman S. Yarkov, Claudio Franceschi, Maria V. Vedunova
Journal: Ageing Research Reviews (2022)